tbuckley/cabot-search huggingface dataset:
Doxorubicin, paclitaxel, and cisplatin (ATP) for refractory germ cell tumors.
Authors: Jenny Jing Xiang, Matthew T Campbell, Shi-Ming Tu, John C. Araujo, Yago Nieto, John Kent Lin, Lianchun Xiao, Amishi Yogesh Shah, Jianbo Wang
Journal: Journal of Clinical Oncology (2023)

e17028 Background: Patients with refractory germ cell tumor (GCT) have limited treatment options and poor prognosis. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient chemotherapy regimen for patients with refractory GCT. Methods: We performed a retrospective chart review of all patients who received ATP at our institution between August 2017 and August 2022. ATP consisted of doxorubicin 30 mg/m2, paclitaxel 100 mg/m2 over one hour, and cisplatin 30 mg/m2 every 2-3 weeks. We reviewed patient and disease characteristics including staging, histology, prior therapies, tumor marker and imaging responses. Progression free survival (PFS) and overall survival (OS) were respectively calculated from the first ATP dose date to disease progression/death and to death/last follow up. Results: A total of 39 patients with refractory GCT received ATP. Patients were 95% male, 54% white, with a mean age of 30 years (range 18-63). Prior to ATP administration, 92% of GCTs had elevated tumor markers, including 54% with elevated AFP, 56% with elevated HCG, and 18% with elevated both tumor markers. 8% of GCTs did not have elevated tumor markers at baseline. Further disease characteristics are described in table 1. Patients received a median of 2 lines of prior systemic therapies (range 1-6), including 97% with prior cisplatin-based regimens and 21% with prior high dose chemotherapy with stem cell rescue transplant. Patients received a median of 3 doses of ATP (range 1-8) with 31% for palliative intent and the rest as a bridge to transplant or other therapies. After ATP administration, 77% patients had decreased tumor markers, including 18% with tumor marker normalization. Of the 19 patients with imaging post-ATP, 53% had complete or partial response, 16% had stable disease, and 32% had disease progression. By December 2022, 79% patients had progression or death, with a median PFS of 3.8 months (95% CI: 1.94, 7.16) and median OS of 10.7 months (95% CI: 6.37, 32.69). 18% of patients experienced toxicities requiring admissions. Conclusions: Based on our retrospective single institution experience, ATP has clinical activity in refractory GCT and is associated with decreased tumor markers and imaging response in most patients. ATP is a convenient and feasible outpatient regimen and can be used in the salvage setting and as a bridge to other therapies. [Table: see text]
Long term follow-up analysis of plasma miR371 expression to detect early relapse in patients with clinical stage I testicular germ cell tumors on surveillance.
Authors: Lucia Nappi, Neetu Saxena, Sara Pautasso, Sylwia Mazurek, Guliz Ozgun, Catarina Kollmannsberger, Max Trottier Chi, Antoine Morin Coulombe, Maryam Soleimani, Kim N. Chi, Bernhard J. Eigl, Peter C. Black, Alan I. So, Martin Gleave, Sean Kern, Siamak Daneshmand, Nabil Adra, Lawrence H. Einhorn, Craig R. Nichols, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2023)

5006 Background: Clinical Stage I (CSI) is the most common presentation of germ cell testicular tumors (GCT) and patients are usually managed with active surveillance, in absence of reliable biomarkers of relapse. Circulating plasma miR371a-3p (miR371) has demonstrated high sensitivity and specificity in advanced non teratoma GCT. However, its operating characteristics and power to detect early relapse are still undefined. Methods: CSI GCT patients enrolled in the British Columbia provincial biobank with available plasma samples after radical orchiectomy were included in this study. Plasma miR371 was qualitatively assessed by RT-PCR. Sensitivity, specificity, negative and positive predictive values (NPV, PPV) and AUC in predicting tumor recurrence were evaluated in the post-orchiectomy blood samples and/or during the follow-up prior to or at the time of the clinically evident relapse. Relapse free survival (RFS) was correlated to post-orchiectomy miR371 status. Results: One-hundred-one patients were analyzed, 35 (34.6%) experienced a disease relapse with a median follow-up of 41 months. miR371 was positive in 22/35 of the relapsed patients. The specificity and PPV were 100% (95% CI: 94.5 - 100 for both), sensitivity 62.8% (95% CI: 44.9 - 78.5), NPV 83.5% (95%CI: 76.7 - 88.6) and AUC 0.81 (95% CI: 0.71 - 0.91). No false positive results were observed. The RFS of the patients with positive post-orchiectomy miR37 was significantly shorter (median: 3.5 months vs. not reached; p&lt;0.0001) compared to the patients with a negative post-orchiectomy miR371 (HR: 16.9; 95% CI: 2.1 - 135.7; p&lt;0.0001). miR371 sensitivity correlated with tumor burden, time between tumor relapse and miRNA testing and histology (nonseminoma &gt; seminoma). Conclusions: miR371 has high specificity and PPV in detecting GCT at an early stage and could be used to predict GCT relapse during surveillance and to guide treatment selection after orchiectomy. Further studies have been planned for validation of miR371 clinical utility.
EXCEED-ET: A single-arm multicenter study to assess the efficacy, safety, and tolerability of ropeginterferon alfa-2b-njft (P1101) in North American adults with essential thrombocythemia.
Authors: Lucia Masarova, John Mascarenhas, Albert Qin, Weichung Shih, Toshiaki Sato, Raymond Urbanski, Oleh Zagrijtschuk, Craig Zimmerman
Journal: Journal of Clinical Oncology (2023)

TPS7088 Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) characterized by a high platelet count due to an overacting JAK-STAT pathway as a result of the most common mutations in JAK2, CALR and MPL genes. There is a high, unmet clinical need for safe and effective treatment options for patients with ET who require cytoreduction, both naïve and previously exposed to hydroxyurea (HU) or anagrelide (ANA). In addition to blood count control and thrombohemorrhagic risk reduction, treatment for ET should also halt/prevent disease progression to post-ET myelofibrosis. Reduction in variant allele frequency and changes in marrow morphology may lead to the elimination of the malignant clone, and treatment with an interferon may achieve this outcome. Interferons have been used in the treatment of MPNs for over 30 years with well-established improvements in hematological and molecular rates, but interferons are not approved by a regulatory agency for the treatment of ET. The objective of this study is to assess the efficacy of ropeginterferon alfa-2b-njft, a new generation interferon alfa, in adults with ET who live in the US or Canada. Methods: This single-arm, open-label study includes a 28-day screening period, a 12-month treatment phase, and a 28-day follow-up period, for a total trial duration of 14 months. An extension phase will supply ropeginterferon alfa-2b-njft to patients deriving benefit for a total of 3 years of treatment. Adults diagnosed with ET according to the WHO 2016 criteria with a platelet count at screening &gt; 450 x 10 9 /L, cytoreductive treatment naïve, or with prior use or currently on HU and/or ANA may participate. Prior treatment with an interferon is an exclusion factor. Patients with a history or presence of clinically relevant depression, risk of suicide, or autoimmune disease may not participate. Ropeginterferon alfa-2b-njft will be administered subcutaneously every 2 weeks at the starting dose of 250 mcg (Week 0), 350 mcg (Week 2), and target dose of 500 mcg (Week 4) and remain fixed for the 12-month treatment period. Subjects currently on HU or ANA will follow a pre-specified dose-tapering schedule. All subjects will receive low-dose aspirin unless contraindicated. The primary endpoint is a durable response defined as the proportion of subjects who achieve simultaneous peripheral blood count remission (platelets ≤400 x10 9 /L and WBC &lt; 10 x 10 9 /L) for at least 80% of bi-weekly measurements consecutively between weeks 32-52, a durable resolution of disease-related symptoms according to the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), and absence of bleeding or thrombotic events. This study is being sponsored by PharmaEssentia USA. Clinical trial information: NCT05482971 .
Molecular profile of SWI/SNF complex in Chinese patients with ovarian cancer.
Authors: Jianmin Li, Tiantian Han, Didi Guo, Rongrong Kong, Siqi Chen, Mengjuan Wang, Yuwei Dong, Ran Ding, Wanglong Deng, Fanfeng Bu, Yang Chen
Journal: Journal of Clinical Oncology (2023)

e17538 Background: The SWI/SNF chromatin remodeling complexes are involved in cancer initiation and progression. ARID1A, ARID1B, and SMARCA4, the essential ATPase subunit of the SWI/SNF chromatin remodeling complex, play important roles in altering chromatin structure for various cellular functions, including transcription, DNA synthesis, and repair. In ovarian cancer (OC), mutations in several SWI/SNF complexes were found, but the molecular and clinical characteristics of SWI/SNF complexes in Chinese ovarian cancer patients have never been reported. Herein, we explored the profiles of SWI/SNF mutation in the Chinese population. Methods: Genetic mutations were reviewed in OC patients who underwent hybridization capture-based next-generation sequencing (NGS). SWI/SNF mutant tumors (MT) were compared to wild-type (WT), and other co-mutations were also evaluated. The pathogenicity of germline mutations was categorized based on American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Among 461 OC patients, mutation in at least one evaluated SWI/SNF gene was identified in 23% of cases. The higher frequency of SWI/SNF alterations were ARID1A (41.03%), ARID1B (13.33%), SMARCA4 (11.28%). The co-mutated genes mainly were TP53, PIK3CA, PTEN. In addition, the MT group tended to have more BRCA1/2 somatic mutations (16.34% vs. 7.84%, χ2＝5.42, p &lt; 0.05) and less BRCA1/2 germline pathogenic mutations (8.7% vs. 17.2%, χ2＝4.40, p &lt; 0.05) compared to WT group. There was a significant statistical difference in TMB value that the MT group was higher than the WT group (11.1 vs. 2.7, p &lt; 0.001). In the MT group, the TMB of patients co-mutated with TP53, PIK3CA, or PTEN mutations were 10.2, 17.3, and 32.3, respectively. The proportion of SWI/SNF alterations in MSI-H tumors was higher than those without mutations (10.0% vs. 0.8%, χ2＝19.29, p &lt; 0.001). Conclusions: SWI/SNF mutant tumors tended to be associated with higher TMB (11.1 vs. 2.7), a higher proportion of MSI-H (10% vs. 0.8%), and more BRCA1/2 somatic mutations ( 16.34% vs. 7.84%) in OC patients. Patients with SWI/SNF alterations combined with PTEN mutation have extremely high TMB (TMB=32.3), indicating they may benefit more from immunotherapy.
Correlations between overall response rate, progression-free survival and overall survival with kinase inhibitors in radioiodine-refractory differentiated thyroid cancers: A systematic review and meta-analysis.
Authors: Nosakhare Paul Ilerhunmwuwa, Mustafa Wasifuddin, Narek Hakobyan, Muhammad Tahir, Boris Avezbakiyev
Journal: Journal of Clinical Oncology (2023)

e18087 Background: Differentiated thyroid cancer (DTC) has a good prognosis; however, about 30% of patients will experience a recurrence after treatment and become refractory to radioiodine therapy. Some studies, including randomized controlled trials (RCTs), have shown the efficacy of kinase inhibitors in these patients, but whether overall response rate (ORR) can predict progression-free survival (PFS) and/or overall survival (OS) has not been well established in the literature. We examined the correlations between ORR and PFS/OS with kinase inhibitors in radioiodine (RAI)-refractory DTC. Methods: PubMed, SCOPUS, Embase, and ClinicalTrials.gov were queried for studies that used kinase inhibitors in RAI-refractory DTC. Eligibility included a clinical diagnosis of RAI-refractory DTC, the use of kinase inhibitors, and articles published in English. ORR, PFS, and OS data were manually retrieved from the studies, and correlative analyses using Spearman's rank correlation coefficient ( r s) were conducted to determine their relationships. Results: Two hundred ninety articles were identified from the literature search; after removing duplicates and screening for relevance and eligibility, 24 studies (6 RCTs and 18 observational), consisting of 1,791 participants, were included for analysis. The kinase inhibitors used were: sorafenib, lenvatinib, donafenib, apatinib, sunitinib, cabozantinib, and vemurafenib. There was no significant correlation between ORR and PFS or OS, and between PFS and OS. However, a sub-analysis of the 6 RCTs (n = 410) alone showed a significantly strong positive correlation between ORR and PFS ( r s = 0.92, p = 0.003) with a 20% increase in ORR corresponding to a prolonged PFS by about five months. No significant correlation was found between any two endpoints in the observational studies. Conclusions: Overall response rate is a predictor of PFS and can be used as a surrogate endpoint for the latter (PFS) in RCTs with kinase inhibitors in RAI-refractory DTC, especially when the time to reach PFS data may be protracted, costly, and delayed treatment. The lack of correlations between ORR and PFS or OS in the observational studies may be due to different populations with varying responses, less controlled settings, time to reach OS data, and probably smaller sample sizes.
Effect of autologous lymphocytes combined with chemotherapy as the first-line treatment of advanced gastric cancer.
Authors: Xiaoting Ma, Lin Yang
Journal: Journal of Clinical Oncology (2023)

4037 Background: To evaluate the safety and initial efficacy of adoptive cell therapy (ACT) combined with SOX in first-line treatment of locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma. Methods: In this single-arm, single-center exploratory trial, patients with histologically confirmed locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma were randomly assigned (1:1) to receive ACT in combination with S-1 and oxaliplatin (SOX) or SOX alone. The primary endpoint was the incidence of adverse events (AEs). Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: Fifty-nine patients were enrolled in the study between November 20, 2014 and September 6, 2017. 31 patients received ACT combined with SOX (ACT-SOX) and 28 patients received SOX. The most common AEs in both groups were gastrointestinal reaction, leucopenia, neutropenia, anemia, thrombocytopenia, hyperbilirubinemia and elevated aspartate transaminase concentration, with a higher incidence in the SOX group. The median PFS for ACT-SOX and SOX were 6.9 and 4.9 months respectively (HR 0.80, p=0.45), and the median OS were 17.8 and 9.75 months (HR 0.76, p=0.34). Patients who received more than three injections of specific lymphocyte subsets benefited the most from combination therapy. Cox univariate and multivariate analysis showed that tumor metastasis to more than two organs was the main risk factor for PFS and OS. 29 patients in the ACT-SOX group and 25 in the SOX group had measurable lesions. The ORR of ACT-SOX group and SOX group was 55.2% and 32.0%, and DCR of two groups was 93.1% and 88.0%. Conclusions: The safety of ACT-SOX in first-line treatment of patients with locally advanced unresectable or metastatic gastric adenocarcinoma/gastroesophageal adenocarcinoma is good. Compared with SOX alone, although the PFS and OS of ACT-SOX did not reach statistical difference, it could further extend the time of PFS and OS, and the absolute improvement time of OS was about 8.05 months. Continuous benefit of ACT-SOX was observed through long-term follow-up. Clinical trial information: NCT02504229 .
Incidence, epidemiological characteristics, and cause-specific survival analysis of ampullary carcinoma using the SEER database.
Authors: Rajvi Gor, Pranav Gwalani, Dhairya Gor, Twinkle Gwalani, Hiba Narvel, Charan Thej Reddy Vegivinti, Sudhamsh Desai, Fnu Vikash, Sindhu Vikash, Hasiya Yusuf, Abhishek Kumar
Journal: Journal of Clinical Oncology (2023)

4168 Background: Ampullary carcinomas (AC) are rare and comprise only 0.2% of gastrointestinal malignancies, and there is a paucity of studies analyzing them. We studied the incidence, demographics, tumor characteristics, and survival variables of patients with AC using the Survival, Epidemiology, and End Results [SEER] November 2021 database. Methods: We identified 3650 patients aged &gt;18 with microscopically confirmed adenocarcinoma of the ampulla using ICD-O-3 site code C241 and histology codes (8140-8147, 8480, 8490, 8500). The epidemiological characteristics and the survival variables included were age, gender, ethnicity, and American Joint Committee on Cancer [AJCC] Staging. The overall 5-year survival (OS), cause-specific 5-year survival (CSS), and CSS plots across different strata were plotted using the Kaplan-Meier Method. The analysis was done using the Cox proportional hazard regression model (p&lt;0.05). Results: The overall age-adjusted incidence of AC was 0.3 per 100,000 cases. The median age at diagnosis was 69 (Interquartile range - 59, 78). It was more common in males (56.03%) and Non-Hispanic White (58.96 %), with the most common stages at a presentation being stage 2B IIB (22.08%) and stage III (22.11%). The observed overall 5-year survival was 31%, and the cause-specific 5-year survival was 37.5%. The CSS was not significantly associated with gender (p=0.06). The estimated hazards of death attributed to AC increase by 13% (p &lt; 0.0001) for every 10-year increase in age at diagnosis above 67 years. The CSS was also associated with race, with African Americans and Hispanics being associated with higher hazards of death attributed to AC when compared to Non-Hispanic Whites with HR of 1.5 (p&lt;0.0001) and 1.12 (p=0.01), respectively. Conclusions: Ampullary carcinoma is more commonly seen in males and non-Hispanic Whites with a median age of 69 years. Patients are typically diagnosed in stages IIB and III. Lower CSS rates were associated with advancing age, African American, and Hispanic populations. We need further studies to determine whether these disparities between different races are due to socioeconomic, genetic, or biological factors. Additional studies investigating how different treatment options affect AC survival, especially in this population subset, can be explored. [Table: see text]
Impact of risk factors on overall survival (OS) in patients (pts) with unresectable hepatocellular carcinoma (HCC) treated with first-line (1L) tislelizumab (TIS).
Authors: Masatoshi Kudo, Richard S. Finn, Tim Meyer, Frederic Boisserie, Songzi Li, Yaxi Chen, Ramil Abdrashitov, Andrew X. Zhu, Arndt Vogel, Shukui Qin
Journal: Journal of Clinical Oncology (2023)

4083 Background: TIS is a monoclonal antibody with high affinity and specificity for programmed cell death protein 1. In the phase 3 RATIONALE-301 trial (NCT03412773), TIS demonstrated non-inferior OS versus sorafenib (SOR) as 1L monotherapy for unresectable HCC (median [m] OS 15.9 [TIS] vs 14.1 [SOR] months [mo]; hazard ratio [HR] 0.85), with a favorable safety profile. Certain biomarkers are potential prognostic factors and may impact OS in 1L treatment of unresectable HCC; this exploratory analysis examined the effect of albumin-bilirubin (ALBI) grade, platelet count, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) as predictors of OS in RATIONALE-301. Methods: Systemic therapy-naïve adults with histologically confirmed HCC (Barcelona Clinic Liver Cancer Stage C or Stage B that was not amenable to or progressed after loco-regional therapy; Child-Pugh A), with ≥1 measurable lesion per RECIST v1.1, and an ECOG performance status ≤1 were randomized 1:1 to receive TIS (200 mg IV Q3W) or SOR (400 mg orally BID) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS. Results: Overall, 674 pts were randomized (TIS n=342; SOR n=332). At data cutoff (July 11, 2022), minimum study follow-up was 33 mo. Demographic and baseline characteristics for biomarkers were generally balanced across arms. Numerically longer (≥2 mo) mOS was observed in biomarker subgroups ALBI grade 1 vs 2 and NLR ≤3 vs &gt;3 with TIS or SOR, and PLR ≤141 vs &gt;141 with TIS. Both platelet count threshold subgroups were accompanied by a smaller difference (&lt;2 mo) in mOS between biomarker cutoffs, which may indicate limited prognostic value for this biomarker. TIS also demonstrated numerically longer OS versus SOR in the same subgroup categories: ALBI grade 1, PLR ≤141, and NLR ≤3. Conclusions: This analysis suggests that ALBI grade, PLR, and NLR could have prognostic value for OS, irrespective of treatment. TIS demonstrated numerically improved mOS compared with SOR for PLR ≤141 and NLR ≤3, suggesting higher benefit for pts with a more favorable balance between systemic inflammation and immunity. Clinical trial information: NCT03412773 . [Table: see text]